This invention relates to novel .beta.-carboline derivatives having an excellent antagonistic acton on cholecystokinin receptors and which are useful for preventing and curing pancreatic disorder and gastrointestinal diseases, and also relates to a process for preparing the same.
Cholecystokinin (CCK) is a brain-gutpeptide existing in the gastrointestinal tract and central nervous system. It has been known as a substance which is concerned with control of pancreatic exocrine secretion and control of appetite, and has been considered to promote the motility of the colon, contract the gallbladder, secrete pancreatic enzymes and inhibit emptying of gastric contents. Further, cholecystokinin coexists with dopamine in a central nervous system so that it has been also considered to have a role concerned with the mechanism of the dopaminergic system.
It has been considered that a substance having an antagonistic action on cholecystokinin receptor is effective for preventing or curing pancreatic disorder and gastrointestinal diseases so that a number of antagonists have been studied up to the present. For example, as a cholecystokinin antagonist, there have been known peptide type antagonistic substances such as benzotrypto. However, such substances are not necessarily satisfactory in that activities thereof are relatively weak, duration of action is short time, and these are unstable and poor in absorption.
As a non-peptide type antagonistic substance, there have been disclosed a benzodiazepine compound in Japanese Provisional Patent Publication No. 111774/1990 and a thienoazepine compound in Japanese Provisional Patent Publication No. 28181/1990. Further, in Japanese Provisional Patent Publication No. 68369/1989, there have been disclosed .beta.-carboline derivatives including a compound of the formula (IV): ##STR2##